The hearts of 8 patients aged 22 to 67 years (mean 41) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in 2 patients, sepsis in 4 patients, acute myocardial infarction in 1, and myocarditis in 1 patient. Transmural left ventricular necrosis was present in 1 of the 2 patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in 5 patients: the inflammatory infiltrate was lymphocytic in 4 and composed of a mixture of eosinophils and lymphocytes in 1. Though treatment related mortality associated with high dose IL-2 therapy is uncommon (1.5% in 652 consecutive patients) the potential for significant myocardial ischemia and/or myocarditis exists and, careful monitoring for arrhythmias and/or myocardial failure is warranted.